title: The central nervous system-restricted transcription factor Olig2 opposes p53 responses to genotoxic damage in neural progenitors and malignant glioma.
abstract: High-grade gliomas are notoriously insensitive to radiation and genotoxic drugs. Paradoxically, the p53 gene is structurally intact in the majority of these tumors. Resistance to genotoxic modalities in p53-positive gliomas is generally attributed to attenuation of p53 functions by mutations of other components within the p53 signaling axis, such as p14(Arf), MDM2, and ATM, but this explanation is not entirely satisfactory. We show here that the central nervous system (CNS)-restricted transcription factor Olig2 affects a key posttranslational modification of p53 in both normal and malignant neural progenitors and thereby antagonizes the interaction of p53 with promoter elements of multiple target genes. In the absence of Olig2 function, even attenuated levels of p53 are adequate for biological responses to genotoxic damage.
authors.affiliation: Department of Cancer Biology, 44 Binney Street, Boston, MA 02115, USA.
authors.forename: Shwetal
authors.initials: S
authors.lastname: Mehta
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Huillard
authors.forename: Santosh
authors.initials: S
authors.lastname: Kesari
authors.forename: Cecile L
authors.initials: CL
authors.lastname: Maire
authors.forename: Diane
authors.initials: D
authors.lastname: Golebiowski
authors.forename: Emily P
authors.initials: EP
authors.lastname: Harrington
authors.forename: John A
authors.initials: JA
authors.lastname: Alberta
authors.forename: Michael F
authors.initials: MF
authors.lastname: Kane
authors.forename: Matthew
authors.initials: M
authors.lastname: Theisen
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.forename: David H
authors.initials: DH
authors.lastname: Rowitch
authors.forename: Charles D
authors.initials: CD
authors.lastname: Stiles
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D005260:Female; D005434:Flow Cytometry; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D016513:Mice, SCID; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism* / Q000528:radiation effects; D000076104:Oligodendrocyte Transcription Factor 2; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D016159:Tumor Suppressor Protein p53; C512773:Olig2 protein, mouse